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A phase i‐ii study of maytansine utilizing a weekly schedule
Author(s) -
Franklin Roman,
Samson Michael K.,
Fraile Roberto J.,
AbuZahra Hakam,
O'bryan Robert,
Baker Laurence H.
Publication year - 1980
Publication title -
cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 3.052
H-Index - 304
eISSN - 1097-0142
pISSN - 0008-543X
DOI - 10.1002/1097-0142(19800901)46:5<1104::aid-cncr2820460505>3.0.co;2-t
Subject(s) - medicine , lethargy , vinca , gastroenterology , adenocarcinoma , subclinical infection , lung cancer , phases of clinical research , toxicity , cancer , pharmacology
Maytansine, a new ansa macrolide antitumor antibiotic, was administered to a total of 107 patients in a Phase I‐II study. Dose‐limiting toxic reactions which occurred at 0.75–1.0 mg/M 2 in both Phase I and II were neurologic and consisted primarily of lethargy/weakness (a debilitation syndrome) and paresthesias. Gastrointestinal and neurologic toxic reactions increased in frequency and severity as a function of dose. Myelosuppression, while infrequent, occurred only in previously treated patients. Changes in liver function tests were subclinical. Two partial remissions were observed at a dose‐level of 0.5 mg/M 2 in Phase I: 1 patient with squamous cell carcinoma of the lung responded for five weeks, while the other patient with adenocarcinoma of the lung responded for four weeks. One partial remission, lasting 14 weeks was seen in Phase II in a patient with malignant melanoma treated at a dose‐level of 1.0 mg/M 2 . All responses were in heavily pretreated patients. Pairs of small bowel biopsy specimen used to define the mitotic index demonstrated peak mitotic arrest at 24 hours in contrast to vinca alkaloids which appear to have a peak mitotic arrest at 12–24 hours.